Kidney Week

Abstract: FR-PO1171

Post-Transplant Thrombotic Microangiopathy with Underlying CFHR1/CFHR3 Deletion: Response to Eculizumab

Session Information

• Transplantation: Clinical - Transplant Access, Recipient Evaluation, Living Donors, Pregnancy, and More
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2002 Transplantation: Clinical

Authors

• Graydon, Drew N., Temple University, Philadelphia, Pennsylvania, United States

Drew N. Graydon, DO

• Patel, Vraj, Temple University, Philadelphia, Pennsylvania, United States

Vraj Patel, MD

• Lee, Iris J., Temple University, Philadelphia, Pennsylvania, United States

Iris J. Lee, MD

• Aggarwal, Kanika, Temple University, Philadelphia, Pennsylvania, United States

Kanika Aggarwal, MD

Introduction

Post transplant thrombotic microangiopathy (TMA) is commonly associated with calcineurin inhibitors (CNI), ischemic reperfusion injury or antibody mediated rejection. Treatment of CNI induced TMA, typically only includes discontinuation of drug. We report a case of severe tacrolimus induced TMA, in a living kidney recipient requiring dialysis, successfully treated with eculizumab and later found to have heterozygous deletion of CFHR1/CFHR3.

Case Description

62-year-old male on peritoneal dialysis (PD) with residual renal function and urine output presented for a living unrelated donor kidney transplant (Tx). Surgery was unremarkable. Post-Tx, patient’s urine output remained unchanged and consistent with residual function (1.5 liter). Creatinine did not improve and remained elevated (10.2 mg/dL). Renal transplant ultrasound showed no significant findings. On Post-op day 5, platelet count was 38K/mm³, haptoglobin <30mg/dL and schistocytes observed on peripheral blood smear, consistent with TMA.
Tacrolimus (Tac) was switched to cyclosporine as he was not a candidate for belatacept (- EBV status). He briefly received plasmapheresis (PP) with IVIG, which was discontinued (ADAMS 13 normal). Cr remained elevated, despite PP/IVIG and Tac discontinuation, and patient started PD. A renal biopsy showed TMA and moderate injury with 40 to 50% interstitial fibrosis. Immunofluorescence was significant for bright C3 staining, raising concern for a complement mediated TMA. Eculizumab was initiated. After two infusions, his creatinine started to improve from 6.46 mg/dl to 2.24 mg/dl. Mayo clinic gene testing showed complement factor H related (CFHR) gene - CFHR1 and CFHR3 heterozygous deletion.

Discussion

CFHR1/CFHR3 deletions impair complement factor H regulation, predisposing to uncontrolled alternative pathway activation. Triggers of complement activation from endothelial injury, like CNI, rejection, reperfusion injury could potentially unmask complement dysregulation in patient with genetic susceptibility. While these mutations are reported as variant of unknown significance (VUS), literature shows reported cases of relation with this gene deletion and complement activation. Complement genetic mutations are identified in up to 60–70% of aHUS cases. Differentiating complement-mediated TMA from other causes is critical, as it guides targeted therapy and beneficial.